Abnormal Recovery from Anesthesia: A Marker of Early Cognitive Dysfunction in Rodent Models of Disease Restricted; Files & ToC
Sinon, Christopher (Fall 2019)
The widespread adoption of general anesthetics in the 19th century led to rapid advancements in surgical practice. However, alongside this growth there has been concern about the appearance of cognitive disturbances in the postoperative period. Large clinical research projects have begun to elucidate some of the risk factors that can predispose patients to postoperative cognitive impairments and correlated the risk for later cognitive impairments with the appearance of earlier postoperative cognitive disturbances. Unfortunately, most published work on abnormal recoveries from anesthesia exists in the form of individual case studies or uses methods that are not currently practical for translation to everyday clinical use. Preclinical models represent a promising approach towards investigating biological underpinnings of abnormal emergence and recovery. This thesis contains our work characterizing the immediate emergence and recovery from anesthesia in preclinical models of conditions known to be risk factors for developing postoperative cognitive impairments. We characterized the behavioral phenotype and neuropathology of a transgenic rat model of Alzheimer’s Disease (AD). At 12-months of age there is neuropathology consistent with the early phase of AD, but with no observed behavioral differences between wild type and transgenic rats. We compared the latency to display emergence and recovery behaviors following isoflurane exposure in 12-month wild type and transgenic rats. Recovery from isoflurane is significantly delayed in transgenic AD rats when compared to wild type. Despite this, transgenic AD rats are not more sensitive to anesthetic drugs as measured by EEG, suggesting that delayed recovery may be due to exacerbation of AD disease pathology. Additionally, we investigated how emergence and recovery behaviors are altered in a type 2 diabetes rat model. We found that these rats do not differ from wild type rats in their emergence or recovery, but prior treadmill exercise hastened recovery from anesthesia in both groups. Overall, we demonstrate the ability to identify changes in the behavioral response to anesthetics in the recovery from general anesthesia due to disease progression and prehabilitative interventions. Our results highlight the need to treat the emergence and recovery from anesthesia as distinct clinical endpoints.
Table of Contents
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